Prostate cancer remains the second most common cause of cancer death among American men. Limitations in prostate imaging technology affect its contribution to clinical assessment and treatment management of prostate cancer. A high tumor cell proliferation rate and cellular density in prostate cancer leads to overall elevated mobile protein and peptide levels. The protein levels in the prostate can be non-invasively detected by a new molecular imaging technique, called amide-proton-transfer magnetic resonance imaging (APT-MRI). APT-MRI will provide efficient measurement for improving our ability to better regionally localize prostate cancer and predict tumor stages. Our preliminary data from 12 prostate cancer patients reveal the increased APT-MRI signal in cancerous regions of the prostate and in higher stage tumors. The preliminary results indicate that the APT-MRI signal is sensitive to the elevated mobile protein and peptide levels in such malignant regions. These initial observations are the basis for a proposed rigorous validation quick trial with a larger and more meaningful number of patients. The overall goal of the quick trial is to evaluate the capability of the APT imaging technique for detection and characterization of prostate cancer. In order to achieve this goal, the proposed quick trial will be implemented within a well-established ongoing collaboration at our Medical Center, which includes urologists performing robotic prostatectomy, pelvic radiologists, MR physicists and technologists, a dedicated pathology team, as well as a biostatistician experienced in the subject matter. In the proposed trial, 66 prostate cancer patients will be imaged with APT-MRI technique, which will give enough power as calculated by our biostatistician. As an additional step, ex-vivo prostate specimen MR imaging will be implemented in order to accurately regionally correlate the histopathology slides with the MRI detectable mobile protein levels. Our hypotheses are: (1) APT-MRI can accurately identify tumors with elevated mobile protein and peptide levels, and (2) the APT-MRI signal is a non-invasive imaging marker to tumor stage based on the amount of detectable mobile protein and peptide levels.
Our specific aims are: (1) to assess the APT- MRI signal in tumor regions as well as in the benign regions, (2) to analyze the APT-MRI signal difference in peripheral zone tumors and transition zone tumors, (3) to evaluate whether APT-MRI can improve prostate cancer detection in addition to dynamic contrast-enhanced MRI, (4) to differentiate non-infiltrating prostate cancer from tumors with extraprostatic extension in clinical tumor staging based on the APT-MRI signal mapping in the prostate, and (5) to identify the tumor extent and staging accuracy from the APT-MRI signal mapping of the prostate by radiologists. This work has the potential to yield a clinically applicable novel MRI technique in prostate cancer imaging field. APT-MRI can be an important quantitative marker to better delineate and detect malignant regions of the prostate in the management of prostate cancer patients.

Public Health Relevance

Prostate cancer remains the second most common cause of cancer death among American men and requires accurate detection for correct management. The goal of this quick trial is to evaluate the capability of a novel protein and peptide-based MRI technique, called amide-proton-transfer (APT) imaging, for better delineation and staging of prostate cancer. Advancing the robust localization of disease extent has the ability to improve nerve sparing with reduced occurrence of erectile dysfunction after prostatectomy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-SBIB-V (56))
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Zhang, Huiming
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Ohio State University
Schools of Medicine
United States
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